Use of pentagastrin to inhibit gastric acid secretion or as a diuretic

a technology of pentagastrin and gastric acid, which is applied in the field of physiological disorders, can solve problems such as ulceration and inflammation of the gastrointestinal tract, and achieve the effects of prolonging the effect, increasing the acid secretion, and increasing the efficacy

Inactive Publication Date: 2008-02-21
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008] Thus, in one embodiment, this invention provides methods of increasing the efficacy of a gastric H+ / K+-ATPase pump inhibitor (PPI) in a mammal (e.g. a rodent, largomorph, bovine, canine, equine, non-human primate, human, etc.). The methods preferably involve administering to the mammal pentagastrin, gastrin or analogues or derivatives thereof in conjunction with a gastric proton pump inhibitor. Pentagastrin is used in particularly preferred embodiments. The pentagastrin can be administered before, simultaneously with, or after the PPI, but in a most preferred embodiment, the pentagastrin administration precedes the PPI administration. In addition to the use of exogenous gastrin or pentagastrin, the method can involve upregulating endogenous gastrin secretion using, for example, aromatic amino acids, or with a meal, etc. Essentially anything that stimulates G-cell activity will increase the efficacy of a PPI.

Problems solved by technology

The mammal may also suffer from hypersensivity to normal acid secretion that may result in gastrointestinal inflammation and ulceration.

Method used

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  • Use of pentagastrin to inhibit gastric acid secretion or as a diuretic
  • Use of pentagastrin to inhibit gastric acid secretion or as a diuretic
  • Use of pentagastrin to inhibit gastric acid secretion or as a diuretic

Examples

Experimental program
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Effect test

example 1

Inhibition of Pentagastrin-Induced Gastric Acid Secretion by Intravenous Pantoprazole: A Dose-Response Study

[0070] The purpose of this study was to compare the gastric acid inhibitory ability of increasing doses of intravenous (i.v.) pantoprazole with that of i.v. famotidine and placebo. Pentagastrin was infused continuously in healthy subjects as a model for patients with Zollinger-Ellison syndrome.

[0071] In brief, pentagastrin (1 μg / kg / h) was infused to stimulate maximum acid output in 39 subjects over a 25-h period. After 60 min of pentagastrin infusion, subjects received a single dose of i.v. pantoprazole (20, 40, 80, or 120 mg), i.v. famotidine (20 mg), or saline placebo. The variables measured were onset of response (time until acid output fell to <10 mEq / h), duration of response (time acid output remained <10 mEq / h), and cumulative acid output over 24 h.

[0072] All doses of i.v. pantoprazole produced a dose-dependent suppression of acid output to 90% in all subjects for <21...

example 2

Discovery of Gastrin Receptors in the Kidney Reveals Hormonal Coupling of Digestion and Excretion

[0102] Ingestion of a meal results in acute changes in renal function necessary to handle absorbed nutrients (Pullman (1954) J. Lab. Clin. Med. 44: 320-332; Jolliffe and Smith (1931) Am. J. Physiol. 99: 101-107; Schoolwerth et al. (1975) Kidney Int. 7: 397-404). However, the mechanism for communication between the digestive and renal systems has never been established. In this example, we report that receptors for gastrin, cholecystokinin type B / gastrin receptors (CCKB / gastrin), are expressed at high levels in the kidney and that gastrin, elevated by either a meal or direct renal infusion, stimulates an increase in urinary Na+ excretion and urine volume that is inhibited by the CCKB / gastrin receptor-specific antagonist, L-365,260 (Lotti and Chang (1989) Eur. J. Pharmacol. 163: 273-279). Gastrin stimulated excretion of sodium and water and its reversal by L-365,260 are paralleled by CCKB...

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Abstract

This invention pertains to the discovery that pentagastrin, when administered in conjunction with a proton pump inhibitor (PPI) is synergistic with the PPI and significantly increases the efficacy of the PPI in reducing / mitigating excess gastric acid secretion.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a Continuation of U.S. Ser. No. 11 / 608,667, filed on Dec. 8, 2006, which is a continuation of U.S. Ser. No. 09 / 671,764, filed on Sep. 27, 2000, which claims priority to and benefit of U.S. Ser. No. 60 / 156,491, filed on Sep. 28, 1999, all of which are incorporated herein by reference in their entirety for all purposes.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT [0002] This invention was made with Government support under a grant awarded by the Veterans Administration. The Government of the United States of America may have certain rights in this invention.FIELD OF THE INVENTION [0003] This invention relates to the treatment of physiological disorders characterized by excess gastric acid secretion. In particular, this invention relates to the use of pentagastrin as a synergist with proton pump inhibitors (PPIs). BACKGROUND OF THE INVENTION [0004] A wide number of patholo...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/16A61K38/08A61P1/00A61K38/22
CPCA61K38/2207A61P1/00
Inventor PISEGNA, JOSEPH R.WANK, STEPHEN
Owner RGT UNIV OF CALIFORNIA
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